Long-term humoral immune responses against SARS-CoV-2 in healthy individuals and patients with primary immunodeficienciess

尽管进行了重症监护治疗，SARS-CoV-2感染仍可能出现轻微症状或最终死亡。因此，人们是否能对SARS-CoV 2的第二次感染产生终身保护以及哪些机制有助于保护的问题是高度相关的，特别是在目前争夺最佳疫苗的背景下。到目前为止，尚未详细研究SARS-CoV-2特异性记忆B细胞的发育，尽管记忆B细胞在恢复期或接种疫苗后对SARS-CoV-2感染过程中发生的冠状病毒诱导的疾病（Covid-19）起主要作用。在这种情况下，目前还不清楚哪些病毒抗原被记忆B细胞识别，多久可以检测到记忆B细胞，以及记忆B细胞的抗原特异性如何与针对SARS-CoV-2的血清抗体和记忆T细胞应答的特异性相关。为了解决这些问题，我们从弗赖堡大学医院的工作人员中建立了一个800多人的队列，其中-正如我们所能显示的那样-大约10%已经暴露于SARS-CoV-2。此外，通过与其他欧洲中心的合作，我们能够创建一个由10名患有明确免疫缺陷综合征的患者组成的小型队列，这些患者在COVID 19中幸存下来。 在这个队列中，我们将在一年的时间内分析SARS-CoV-2反应性记忆B细胞的亚群、特异性、频率和寿命。在免疫缺陷患者队列中，我们计划研究病毒特异性B和T细胞对冠状病毒感染的反应的形成和亚群特征，以及与免疫活性供体的潜在差异。一旦SARS-CoV-2疫苗可用，我们计划对接种疫苗的个体进行这些研究，并将结果与研究SARS-CoV-2感染的康复者获得的数据进行比较。我们希望我们的方法将允许确定感染和疫苗接种导致持久的B细胞记忆的程度，这种记忆可以防止SARS-CoV-2再次感染导致的Covid-19。这与记忆性T细胞反应的发展如何相关，并了解哪些参数与强烈的记忆反应最相关。这种方法将有望使我们能够为PAD/CVID患者开发针对SARS-CoV-2的疫苗接种的合适策略，并调查他们随时间的免疫应答。

SARS-CoV-2 infections can remain oligosymptomatic or end fatally despite of intensive care treatment. Therefore, the question whether one develops a lifelong protection against a second infection by SARS-CoV2 and which mechanisms contribute to the protection is highly relevant, especially also in the context of the current race for the best vaccine. So far, the development of SARS-CoV-2 specific memory B cells has not been studied in detail although memory B cells contribute essentially after convalescence or after vaccination against the coronavirus-induced disease (Covid-19) which develops in the course of SARS-CoV-2 infections. In this context, it is unclear which viral antigens are recognized by memory B cells, how long memory B cells can be detected and how the antigen specificity of memory B cells correlates with the specificity of serum antibodies and memory T cell responses directed against SARS-CoV-2. To approach these questions, we have established a cohort of more than 800 persons from the staff of the University Hospital Freiburg, of which - as we have been able show - about 10% have been exposed to SARS-CoV-2. In addition, in collaboration with other European centers we were able to create a small cohort of 10 patients with defined immunodeficiency syndromes, who have survived COVID19. In this cohorts we will analyze the subsets, specificity, frequency and longevity of SARS-CoV-2 reactive memory B cells over the time period of one year. In the cohort of immunodeficient patients we plan to investigate the formation and subset characteristics of virus-specific B- and T-cells in response to coronavirus infection as well as potential differences to immunocompetent donors. Once vaccinations against SARS-CoV-2 are available, we plan to carry out these studies with vaccinated individuals and compare the results with the data obtained from studying convalescents from SARS-CoV-2 infections. We hope that our approach will allow to determine the extent to which infections and vaccinations lead to a long-lasting B cell memory which can protect against Covid-19 resulting from re-infection with SARS-CoV-2., how this correlates with the development of a memory T cell response and to understand, which parameters correlate the best with a strong memory response.This approach will hopefully allow us to develop suitable strategies for vaccination against SARS-CoV-2 for PAD/CVID patients and survey their immune response over time.